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In human, intradermal administration of β-alanine (ALA) and bovine adrenal medulla peptide 8-22 (BAM8-22) evokes the sensation of itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express the receptors of these pruritogens, MRGPRD and MRGPRX1 respectively, and which cutaneous afferents these pruritogens activate in primate. In situ hybridization studies revealed that MRGPRD and MRGPRX1 are co-expressed in a subpopulation of TRPV1+ human DRG neurons. In electrophysiological recordings in nonhuman primates (Macaca nemestrina), subtypes of polymodal C-fiber nociceptors are preferentially activated by ALA and BAM8-22, with significant overlap. When pruritogens ALA, BAM8-22 and histamine, that activate different subclasses of C-fiber afferents, are administered in combination, human volunteers report itch and nociceptive sensations similar to those induced by a single pruritogen. Our results provide evidence for differences in pruriceptive processing between primates and rodents, and do not support the spatial contrast theory of coding of itch and pain.

BackgroundThe COVID-19 pandemic has impacted people with substance use disorders (SUDs) worldwide and healthcare systems have reorganized their services in response to the pandemic.MethodsOne week after the announcement of the COVID-19 as a pandemic, in a global survey, 177 addiction medicine professionals described COVID-19-related health responses in their own 77 countries in terms of SUD treatment and harm reduction services. The health response is categorized around (1) managerial measures and systems, (2) logistics, (3) service providers and (4) vulnerable groups.ResultsRespondents from over 88% of countries reported that core medical and psychiatric care for SUDs had continued; however, only 56% of countries reported having had any business continuity plan, and, 37.5% of countries reported shortages of methadone or buprenorphine supplies. Participants of 41% of countries reported partial discontinuation of harm-reduction services such as needle and syringe programs and condom distribution. 57% of overdose prevention interventions and 81% of outreach services also having been negatively impacted.ConclusionsParticipants reported that SUD treatment and harm reduction services had been significantly impacted globally early during the COVID-19 pandemic. Based on our findings, we provide a series of recommendations to support countries to be prepared more efficiently for future waves or similar pandemics to 1) help policymakers generate business continuity plans, 2) maintain use of evidence-based interventions for people with SUDs, 3) be prepared for adequate medication supplies, 4) integrate harm reduction programs with other treatment modalities and 5) have specific considerations for vulnerable groups such as immigrants and refugees.HighlightsCOVID-19 negatively impacted services for PWSUD globally.Addiction medicine downgraded more than other psychiatry services.Business continuity plan for PWSUD services reported only in about half of the countries.Refugees & migrants had more negative impact compared to other vulnerable groups.Harm reduction services discontinued partially or totally during pandemic.

Background and aimsCOVID-19 has infected more than 13 million people worldwide and impacted the lives of many more, with a particularly devastating impact on vulnerable populations, including people with substance use disorders (SUDs). Quarantines, travel bans, regulatory changes, social distancing and ‘lockdown’ measures have affected drug and alcohol supply chains and subsequently their availability, price and use patterns, with possible downstream effects on presentations of SUDs and demand for treatment. Given the lack of multicentric epidemiologic studies, we conducted a rapid global survey within the International Society of Addiction Medicine (ISAM) network in order to understand the status of substance-use patterns during the current pandemic.DesignCross-sectional survey.SettingWorldwide.ParticipantsStarting on April 4th, 2020 during a 5-week period, the survey received 185 responses from 77 countries.MeasurementsTo assess addiction medicine professionals’ perceived changes in drug and alcohol supply, price, use pattern and related complications during the COVID-19 pandemic.FindingsParticipants reported (among who answered “decreased” or “increased”, percentage of those who were in majority is reported in the parenthesis) a decrease in drug supply (69.0%), and at the same time an increase in price (95.3%) globally. With respect to changes in use patterns, an increase in alcohol (71.7%), cannabis (63.0%), prescription opioids (70.9%), and sedative/hypnotics (84.6%) use was reported while the use of amphetamines (59.7%), cocaine (67.5%), and opiates (58.2%) was reported to decrease overall.ConclusionsThe global report on changes in the availability, use patterns and complications of alcohol and drugs during the COVID-19 pandemic should be considered in making new policies and in developing mitigating measures and guidelines during the current pandemic (and probable future ones) in order to minimize risks to SUDs.Competing interestAuthors claimed no competing interest

Chronic and recurrent opiate use injuries brain tissue and cause serious pathophysiological changes in hemodynamic and subsequent inflammatory responses. Prefrontal cortex (PFC) has been implicated in drug addiction. However, the mechanism underlying systems-level neuroadaptations in PFC during abstinence has not been fully characterized. The objective of our study was to determine what neural oscillatory activity contributes to the chronic effect of opiate exposure and whether the activity could be coupled to neurovascular information in the PFC. We employed resting-state functional connectivity to explore alterations in 8 patients with heroin dependency who stayed abstinent (>3 months; HD) compared with 11 control subjects. A non-invasive neuroimaging strategy was applied to combine electrophysiological signals through electroencephalography (EEG) with hemodynamic signals through functional near-infrared spectroscopy (fNIRS). The electrophysiological signals indicate neural synchrony and the oscillatory activity, and the hemodynamic signals indicate blood oxygenation in small vessels in the PFC. A supervised machine learning method was used to obtain associations between EEG and fNIRS modalities to improve precision and localization. HD patients demonstrated desynchronized lower alpha rhythms and decreased connectivity in PFC networks. Asymmetric excitability and cerebrovascular injury were also observed. This pilot study suggests that cerebrovascular injury in PFC may result from chronic opiate intake.

Functional near-infrared spectroscopy (fNIRS) has emerged as a highly promising brain mapping technique that enables continuously and noninvasively monitoring the hemodynamic responses in the human brain. In this study, fNIRS was utilized to identify the different brain activation patterns between pathological gamblers (PGs) and healthy controls (HCs). Specifically, we examined the hemodynamic changes in the prefrontal cortex using fNIRS recordings during the completion of executive function and decision-making tasks for both PGs and HCs. Our mapping results revealed that PGs and HCs exhibited notable differences in the hemodynamic responses and brain activation patterns across the prefrontal region.

Drug addiction is widely linked to the orbitofrontal cortex (OFC), which is essential for regulating reward-related behaviors, emotional responses, and anxiety. Over the past two decades, neuroimaging has provided significant contributions revealing functional and structural alternations in the brains of drug addicts. However, the underlying neural mechanism in the OFC and its correlates with drug addiction and anxiety still require further elucidation. We first presented a pilot investigation to examine local networks in OFC regions through resting-state functional connectivity (rsFC) using functional near-infrared spectroscopy (fNIRS) from eight abstinent addicts in a heroin-dependent group (HD) and seven subjects in a control group (CG). We discovered that the HDs manifested enhanced interhemispheric correlation and rsFC. Moreover, small-worldness was explored in the brain networks. In addition to the altered rsFC in the OFC networks, our examinations demonstrated associations in the functional connectivity between the left inferior frontal gyrus and other OFC regions related to anxiety in the HDs. The study provides important preliminary evidence of the complex OFC networks in heroin addiction and suggests neural correlates of anxiety. It opens a window in application of fNIRS to predict psychiatric trajectories and may create new insights into neural adaptations resulting from chronic opiate intake.

Dependence to opiates, including illicit heroin and prescription pain killers, and treatment of the opioid use disorder (OUD) have been longstanding problems over the world. Despite intense efforts to scientific investigation and public health care, treatment outcomes have not significantly improved for the past fifty years. One reason behind the continuing use of heroin worldwide despite such efforts is its highly addictive nature. Brain imaging studies over the past two decades have made significant contribution to the understanding of the addictive properties as to be due in part to biological processes, specifically those in the brain structurally and functionally. Moreover, traditional clinical neuropsychology studies also contribute to the account in part for the treatment-refractory nature of the drug abuse. However, there is a gap between those studies, and the rates of relapse are still high. Thus, a multidisciplinary approach is needed to understand the fundamental neural mechanism of OUD. How does the brain of an OUD patient functionally and cognitively differ from others? This brief review is to compare and contrast the current literature on non-invasive resting state neuroimaging and clinical neuropsychological studies with the focus on the abstinence stage in OUD. The results show as follow: 1. Brain connectivity strength in the reward system, dysregulation of circuits associated with emotion and stress, enhanced beta and alpha power activity, and high impulsivity are induced by OUD. 2. Recovery signs in cognition are demonstrated in OUD subjects after prolonged abstinence, but not in the subjects undergoing methadone treatment. 3. Normalization in the composition of brain oscillations especially in the temporal region is induced and restored by methadone treatment in roughly 6 months in mean duration for OUDs having a mean opioid-use history of 10 years. We hope that the review provides valuable implications for clinical research and practice and paves a new insight into the future path to the identification of potential biomarkers and clinical outcome predictors in OUD in the domains of brain regions, functions, and behaviors.